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International Journal of Molecular... Jun 2024The continuously expanding field of Alzheimer's disease (AD) research is now beginning to defocus the brain to take a more systemic approach to the disease, as...
Glomerular Hypertrophy and Splenic Red Pulp Degeneration Concurrent with Oxidative Stress in 3xTg-AD Mice Model for Alzheimer's Disease and Its Exacerbation with Sex and Social Isolation.
The continuously expanding field of Alzheimer's disease (AD) research is now beginning to defocus the brain to take a more systemic approach to the disease, as alterations in the peripheral organs could be related to disease progression. One emerging hypothesis is organ involvement in the process of Aβ clearance. In the present work, we aimed to examine the status and involvement of the kidney as a key organ for waste elimination and the spleen, which is in charge of filtering the blood and producing lymphocytes, and their influence on AD. The results showed morphological and structural changes due to acute amyloidosis in the kidney (glomeruli area) and spleen (red pulp area and red/white pulp ratio) together with reduced antioxidant defense activity (GPx) in 16-month-old male and female 3xTg-AD mice when compared to their age- and sex-matched non-transgenic (NTg) counterparts. All these alterations correlated with the anxious-like behavioral phenotype of this mouse model. In addition, forced isolation, a cause of psychological stress, had a negative effect by intensifying genotype differences and causing differences to appear in NTg animals. This study further supports the relevance of a more integrative view of the complex interplay between systems in aging, especially at advanced stages of Alzheimer's disease.
Topics: Animals; Alzheimer Disease; Oxidative Stress; Mice; Disease Models, Animal; Male; Social Isolation; Female; Mice, Transgenic; Spleen; Kidney Glomerulus; Hypertrophy
PubMed: 38892297
DOI: 10.3390/ijms25116112 -
International Journal of Molecular... May 2024Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in...
Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in BALB/C WT mice, we examined metformin's impact on the functional phenotype of multiple immune cells, with a specific emphasis on natural killer T (NKT) cells due to their understudied role in this context. Metformin administration delayed the appearance and growth of carcinoma. Furthermore, metformin increased the percentage of IFN-γ NKT cells, and enhanced CD107a expression, as measured by MFI, while decreasing PD-1, FoxP3, and IL-10 NKT cells in spleens of metformin-treated mice. In primary tumors, metformin increased the percentage of NKp46 NKT cells and increased FasL expression, while lowering the percentages of FoxP3, PD-1, and IL-10-producing NKT cells and KLRG1 expression. Activation markers increased, and immunosuppressive markers declined in T cells from both the spleen and tumors. Furthermore, metformin decreased IL-10 and FoxP3 Tregs, along with Gr-1 myeloid-derived suppressor cells (MDSCs) in spleens, and in tumor tissue, it decreased IL-10 and FoxP3 Tregs, Gr-1, NF-κB, and iNOS MDSCs, and iNOS dendritic cells (DCs), while increasing the DCs quantity. Additionally, increased expression levels of MIP1a, STAT4, and NFAT in splenocytes were found. These comprehensive findings illustrate metformin's broad immunomodulatory impact across a variety of immune cells, including stimulating NKT cells and T cells, while inhibiting Tregs and MDSCs. This dynamic modulation may potentiate its use in cancer immunotherapy, highlighting its potential to modulate the tumor microenvironment across a spectrum of immune cell types.
Topics: Metformin; Animals; Female; Mice; Breast Neoplasms; Mice, Inbred BALB C; Cell Line, Tumor; Myeloid-Derived Suppressor Cells; Natural Killer T-Cells; T-Lymphocytes, Regulatory; Immunomodulating Agents
PubMed: 38892058
DOI: 10.3390/ijms25115869 -
International Journal of Molecular... May 2024Dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) has been found to be beneficial in rodent rheumatoid arthritis models and human trials. However, the...
Dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) has been found to be beneficial in rodent rheumatoid arthritis models and human trials. However, the molecular targets of n-3 PUFAs and their beneficial effects on rheumatoid arthritis are under-researched. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor for n-3 PUFA. We aim to investigate whether FFA4 activation reduces collagen-induced rheumatoid arthritis (CIA) by using an FFA4 agonist, compound A (CpdA), in combination with DBA-1J gene wild-type (WT) and gene knock-out (KO) mice. CIA induced an increase in the arthritis score, foot edema, synovial hyperplasia, pannus formation, proteoglycan loss, cartilage damage, and bone erosion, whereas the administration of CpdA significantly suppressed those increases in WT mice but not gene KO mice. CIA increased mRNA expression levels of pro-inflammatory Th1/Th17 cytokines, whereas CpdA significantly suppressed those increases in WT mice but not gene KO mice. CIA induced an imbalance between Th1/Th17 and Treg cells, whereas CpdA rebalanced them in spleens from WT mice but not gene KO mice. In SW982 synovial cells, CpdA reduced the LPS-induced increase in pro-inflammatory cytokine levels. In summary, the present results suggest that the activation of FFA4 in immune and synovial cells could suppress the characteristics of rheumatoid arthritis and be an adjuvant therapy.
Topics: Animals; Arthritis, Experimental; T-Lymphocytes, Regulatory; Th17 Cells; Receptors, G-Protein-Coupled; Mice; Th1 Cells; Mice, Knockout; Mice, Inbred DBA; Arthritis, Rheumatoid; Male; Cytokines
PubMed: 38892051
DOI: 10.3390/ijms25115866 -
International Journal of Molecular... May 2024While considerable attention has been devoted to respiratory manifestations, such as pneumonia and acute respiratory distress syndrome (ARDS), emerging evidence...
While considerable attention has been devoted to respiratory manifestations, such as pneumonia and acute respiratory distress syndrome (ARDS), emerging evidence underlines the significance of extrapulmonary involvement. In this study, we examined 15 hospitalized patients who succumbed to severe complications following SARS-CoV-2 infection. These patients were admitted to the Sibiu County Clinical Emergency Hospital in Sibiu, Romania, between March and October 2021. All patients were ethnic Romanians. Conducted within a COVID-19-restricted environment and adhering to national safety protocols, autopsies provided a comprehensive understanding of the disease's multisystemic impact. Detailed macroscopic evaluations and histopathological analyses of myocardial, renal, hepatic, splenic, and gastrointestinal tissues were performed. Additionally, reverse transcription-quantitative polymerase chain reaction (rt-qPCR) assays and immunohistochemical staining were employed to detect the viral genome and nucleocapsid within the tissues. Myocardial lesions, including ischemic microstructural changes and inflammatory infiltrates, were prevalent, indicative of COVID-19's cardiac implications, while renal pathology revealed the chronic alterations, acute tubular necrosis, and inflammatory infiltrates most evident. Hepatic examination identified hepatocellular necroinflammatory changes and hepatocytic cytopathy, highlighting the hepatic involvement of SARS-CoV-2 infection. Splenic parenchymal disorganization was prominent, indicating systemic immune dysregulation. Furthermore, gastrointestinal examinations unveiled nonspecific changes. Molecular analyses detected viral genes in various organs, with immunohistochemical assays confirming viral presence predominantly in macrophages and fibroblasts. These findings highlighted the systemic nature of SARS-CoV-2 infection, emphasizing the need for comprehensive clinical management strategies and targeted therapeutic approaches beyond respiratory systems.
Topics: Humans; SARS-CoV-2; COVID-19; Male; Female; Middle Aged; Genome, Viral; Aged; Kidney; Liver; Adult; Spleen; Romania; Nucleocapsid; Myocardium; Autopsy; Aged, 80 and over; Coronavirus Nucleocapsid Proteins
PubMed: 38891942
DOI: 10.3390/ijms25115755 -
International Journal of Molecular... May 2024Functional foods enriched with plant polyphenol anthocyanins attract particular attention due to their health-promoting properties, including antitumor activity. We...
Functional foods enriched with plant polyphenol anthocyanins attract particular attention due to their health-promoting properties, including antitumor activity. We evaluated the effects of a grain diet rich in anthocyanins in a mouse model of Lewis lung carcinoma. Mice of the C57BL/6 strain were fed with wheat of near-isogenic lines differing in the anthocyanin content for four months prior to tumor transplantation. Although a significant decrease in the size of the tumor and the number of metastases in the lungs was revealed in the groups with both types of grain diet, the highest percentage of animals without metastases and with attenuated cell proliferation in the primary tumor were observed in the mice with the anthocyanin-rich diet. Both grain diets reduced the body weight gain and spleen weight index. The antitumor effects of the grain diets were associated with the activation of different mechanisms: immune response of the allergic type with augmented interleukin(IL)-9 and eotaxin serum levels in mice fed with control grain vs. inhibition of the IL-6/LIF system accompanied by a decrease in the tumor-associated M2 macrophage marker arginase 1 gene mRNA levels and enhanced autophagy in the tumor evaluated by the mRNA levels of Beclin 1 gene. Thus, anthocyanin-rich wheat is suggested as a promising source of functional nutrition with confirmed in vivo antitumor activity.
Topics: Animals; Anthocyanins; Carcinoma, Lewis Lung; Mice; Mice, Inbred C57BL; Disease Models, Animal; Diet; Cell Proliferation; Lung Neoplasms; Edible Grain; Antineoplastic Agents; Triticum
PubMed: 38891915
DOI: 10.3390/ijms25115727 -
International Journal of Molecular... May 2024Heat shock proteins (HSPs) are a class of highly conserved proteins that play an important role in biological responses to various environmental stresses. The...
Heat shock proteins (HSPs) are a class of highly conserved proteins that play an important role in biological responses to various environmental stresses. The mariculture of , a burgeoning aquaculture species in China, frequently encounters stressors such as extreme temperatures, salinity variations, and elevated ammonia levels. However, systematic identification and analysis of the HSP70 and HSP90 gene families in remain unexplored. This study conducted the first genome-wide identification of 12 HSP70 and 4 HSP90 genes in , followed by a comprehensive analysis including phylogenetics, gene structure, conserved domains, chromosomal localization, and expression profiling. Expression analysis from RNA-seq data across various tissues and developmental stages revealed predominant expression in muscle, spleen, and liver, with the highest expression found during the tailbud stage, followed by the gastrula, neurula, and juvenile stages. Under abiotic stress, most HSP70 and HSP90 genes were upregulated in response to high temperature, high salinity, and low salinity, notably during thermal stress, in high salinity, and under low salinity conditions. Ammonia stress led to a predominance of downregulated HSP genes in the liver, particularly , while upregulation was observed in the gills, especially for . Quantitative real-time PCR analysis corroborated the expression levels under environmental stresses, validating their involvement in stress responses. This investigation provides insights into the molecular mechanisms of HSP70 and HSP90 in under stress, offering valuable information for future functional studies of HSPs in teleost evolution, optimizing aquaculture techniques, and developing stress-resistant strains.
Topics: Animals; Phylogeny; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Stress, Physiological; Fish Proteins; Multigene Family; Gene Expression Profiling; Fishes; Salinity
PubMed: 38891896
DOI: 10.3390/ijms25115706 -
International Journal of Molecular... May 2024Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA)...
Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA) compound ([At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [At]PSMA-5 was administered to both normal male ICR mice ( = 85) and cynomolgus monkeys ( = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day ( = 10 per group) and 14 days ( = 5 per group). Monkeys were observed 24 h post-administration of [At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of At using a cyclotron supports its applicability for clinical use.
Topics: Animals; Male; Prostatic Neoplasms; Mice; Tissue Distribution; Mice, Inbred ICR; Astatine; Alpha Particles; Humans; Macaca fascicularis; Glutamate Carboxypeptidase II; Radiopharmaceuticals
PubMed: 38891856
DOI: 10.3390/ijms25115667 -
Animals : An Open Access Journal From... Jun 2024Myelolipoma is a benign, typically inert neoplasm of uncertain aetiology that is rarely reported in cats. Although commonly asymptomatic, in some cases, myelolipomas can...
Myelolipoma is a benign, typically inert neoplasm of uncertain aetiology that is rarely reported in cats. Although commonly asymptomatic, in some cases, myelolipomas can cause abdominal discomfort or present with rupture and haemorrhage. Here, we describe a rare case of a splenic myelolipoma in a Domestic Long Hair cat in which, after extensive diagnostic investigations, clinical signs of hyporexia and weight loss were attributable to the presence of an intra-abdominal mass. The patient was treated by splenectomy and unexpectedly died during the post-operative period. Although splenectomy appears to be a sensible intervention in symptomatic patients, the optimal management of splenic myelolipomas in cats remains unknown. The risk-benefit ratio of surgical management needs to be carefully considered, and therapeutic intervention should be tailored individually to each patient.
PubMed: 38891746
DOI: 10.3390/ani14111700 -
Animals : An Open Access Journal From... Jun 2024This study evaluated the effects of GT001 on ()-challenged broiler chickens. Two hundred Ross 708 broiler day-old chicks with comparable weight were distributed at...
This study evaluated the effects of GT001 on ()-challenged broiler chickens. Two hundred Ross 708 broiler day-old chicks with comparable weight were distributed at random into four treatments with five replicates and ten chicks per replicate. The following were the treatment groups: (B) basal diet (control); (B + S) basal diet and birds were challenged with at 1.0 × 10 cfu/g; (B + P) basal diet + GT001 at 4.0 × 10 cfu/g; (B + P + S) basal diet + GT001 at 4.0 × 10 cfu/g and birds were challenged with at 1.0 × 10 cfu/g. There was a significant reduction ( < 0.05) in the body weight of the -infected birds compared to the other treatment groups. However, the FCRs of the broilers were comparable among the different treatment groups ( > 0.05). The lipid profile and liver function indices measured were significantly enhanced in the GT001-supplemented groups (B + P and B + P + S) compared to the group that was -challenged ( < 0.05) but were similar to those in the control group. The serum antioxidant activities, such as the T-AOC, SOD, CAT, GHS-Px and MDA, were significantly improved in the GT001-supplemented groups (B + P and B + P + S) ( < 0.05). The MDA was similar in the B + P and B + P + S groups, but both were significantly lower than the control and the groups. The administration of GT001 enhanced the lipase and amylase levels in both the serum and intestine of the broilers ( < 0.05). The immunoglobin (IgA, IgG, IgM) and cytokine (IL-10 and IL-6) levels in the serum were significantly higher in the B, B + P and B + P + S treatment groups ( < 0.05). The immune-related organs (bursa and spleen) were significantly influenced in the birds fed with GT001. No significant variation was noted among all the dietary treatments in terms of the measured meat quality indices. The small intestinal digesta content of the load was below a detectable range after 14 days of infection ( < 0.05). No significant differences were observed among the different treatment groups in terms of the breast pH, drip loss and meat color ( > 0.05). The inclusion of GT001 also modified the community structure in the cecum. This indicates that it has health benefits and could be incorporated in the broiler diet.
PubMed: 38891723
DOI: 10.3390/ani14111676 -
Animals : An Open Access Journal From... May 2024The experiment aimed to investigate the effects of plant polysaccharides combined with boric acid on digestive function, immune function and harmful gas and heavy metal...
The experiment aimed to investigate the effects of plant polysaccharides combined with boric acid on digestive function, immune function and harmful gas and heavy metal contents in the faeces of fatteners. For this study, 90 healthy crossbred fatteners were selected and randomly divided into five groups: the control group was fed with a basal diet (Con); experimental group I was fed with basal diet + 40 mg/kg boric acid (BA); experimental group II was fed with basal diet + 40 mg/kg boric acid + 400 mg/kg polysaccharides (BA+APS); experimental group III was fed with basal diet + 40 mg/kg boric acid + 200 mg/kg polysaccharides (BA+GLP); and experimental group IV was fed with basal diet + 40 mg/kg boric acid + 500 mg/kg polysaccharides (BA+EPS). Compared with Con, the average daily gain (ADG), the trypsin activities in the duodenum and jejunum, the IL-2 levels in the spleen, the T-AOC activities and GSH-Px contents in the lymph node of fattening were increased in the BA group ( < 0.05), but malondialdehyde content in the lymph and spleen, and the contents of NH, HS, Hg, Cu, Fe and Zn in the feces and urine were decreased ( < 0.05). Compared with the BA, the ADG, gain-to-feed ratio (G/F), the trypsin and maltase activities in the duodenum and jejunum were increased in the BA+APS ( < 0.05), and the T-SOD activities in the spleen and T-AOC activities in the lymph node were also increased ( < 0.05), but the HS level was decreased in the feces and urine ( < 0.05). Compared with the BA, the ADG, G/F and the trypsin and maltase activities in the duodenum were increased in the BA+GLP and BA+EPS ( < 0.05), the activities of maltase and lipase in the duodenum of fatteners in the BA+GLP and the activities of trypsin, maltase and lipase in the BA+EPS were increased ( < 0.05). Gathering everything together, our findings reveal that the combined addition of boric acid and plant polysaccharides in the diet of fatteners synergistically improved their growth performance and immune status. That may be achieved by regulating the activity of intestinal digestive enzymes, improving the antioxidant function and then promoting the digestion and absorption of nutrients. Furthermore, the above results reduce the emission of harmful gases and heavy metals in feces and urine.
PubMed: 38891562
DOI: 10.3390/ani14111515